Is SRRT p.Ile618Met (c.1854C>G) pathogenic?

SRRT p.Ile618Met (c.1854C>G) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: ambiguous (0.3897); Very rare (popmax 0.00534%, afr).

How common is SRRT p.Ile618Met (c.1854C>G) in the general population?

SRRT p.Ile618Met (c.1854C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about SRRT p.Ile618Met (c.1854C>G)?

AlphaMissense predicts ambiguous (score 0.3897) — an in-silico prediction, not a clinical call.

SRRT p.Ile618Met

c.1854C>G · rs765305318 · VCV2558105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3897 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Computational evidence

Protein change
AlphaMissense	0.3897	ambiguous
REVEL	0.417	indeterminate
SaProt	LLR -11.05	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -5.1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,248 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	0.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,954 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000496% 8/1,614,122 alleles · very rare exomes 4/1,461,890 · genomes 4/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,738
European (non-Finnish)	0.000339%	295,013

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SRRT
Protein: p.Ile618Met
Coding: c.1854C>G
MANE Select: NM_015908
dbSNP: rs765305318
Type: single nucleotide variant
Location: chr7:100887079 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 618: an α-helix

Full SRRT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRRT p.Ile618Val Uncertain significance ★ ⚠ same residue
SRRT c.1042-18C>G Benign ★★ same type
SRRT c.1042-7C>T Benign ★★ same type
SRRT c.2556-9A>T Benign ★★ same type
SRRT p.Arg518= Benign ★★ same type
SRRT p.Glu205= Benign ★★ same type
SRRT p.Leu157= Benign ★★ same type
SRRT p.Leu265= Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/srrt-p-ile618met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown